1. Field of the Invention
The present invention is directed to the purification of aminophosphonic acids More particularly, the present invention relates to the purification of aminophosphonic acid compounds, such as ethylenediamine tetra(methylene phosphonic acid) (EDTMP), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP), diethylenetriamine penta(methylene phosphonic acid) (DTPMP), nitrilo tri(methylene phosphonic acid) (NTMP), hydroxyethylethylenediamine tri(methylene phosphonic acid) (HEEDTMP), tris(2-aminoethyl)aminehexa (methylene phosphonic acid) (TTHMP), and the like, by adding the crude, unpurified aminophosphonic acid to water at neutral or acidic pH to form a slurry that is then heated to reflux, cooled to approximately 80.degree. C., and filtered.
2. Discussion of the Background
Aminophosphonic acids and their salts are well-known chelating agents for metal ions. Depending upon the properties of the metal ion to be complexed, the resulting metal-aminophosphonic acid complex may be used to treat tumors, to enhance a magnetic resonance image, a sonographic image, an X-ray image, and the like. Of course, aminophosphonic acid chelating agents are also useful in more traditional chelation technologies such as scale removal, water-softening, ore leaching, textile processing, food preservation, the treatment of lead poisoning, chemical analysis, and the like.
The preparation and use of aminophosphonic acids has been described. For example, Krueger et al. describe a process for producing aminoalkylene phosphonic acids by reacting alkylene glycol chlorophosphites with an aldehyde or ketone and an amine or an acid addition salt thereof or an acid amide of a lower mono- or dicarboxylic acid (see U.S. Pat No. 3,832,393, incorporated herein by reference). Garlich et al. disclose a method for purifying aminomethylenephosphonic acids for pharmaceutical use in which the aminomethylene phosphonic acid is dissolved in aqueous base, and the solution is added to an acid solution maintained at elevated temperature to precipitate the aminophosphonic acid (see U.S. Pat. No. 4,937,333, incorporated herein by reference).
As described above, aminophosphonic acids may be employed in therapeutic or pharmaceutical formulations. Thus, the purity of the aminophosphonic acid must be such that it is suitable for administration to humans. The production of pharmaceutical-grade products is an on-going and well-known problem in the pharmaceutical art, and the reduction and/or elimination of impurities from therapeutic or pharmaceutical products, including formulations, is a constant concern.